HLA-A is a Predictor of Hepatitis B e Antigen Status in HIV-Positive African Adults

Abstract

Outcomes of chronic infection with hepatitis B virus (HBV) are varied, with increased morbidity reported in the context of human immunodeficiency virus (HIV) coinfection. The factors driving different outcomes are not well understood, but there is increasing interest in an HLA class I effect. We therefore studied the influence of HLA class I on HBV in an African HIV-positive cohort. We demonstrated that virologic markers of HBV disease activity (hepatitis B e antigen status or HBV DNA level) are associated with HLA-A genotype. This finding supports the role of the CD8(+) T-cell response in HBV control, and potentially informs future therapeutic T-cell vaccine strategies.

Keywords: Africa; CD8+ T cells; HBV; HBeAg (hepatitis B e antigen); HIV; HLA; coinfection; immunology; viral hepatitis.

Figure 1.

Receiver operating characteristic (ROC) curves for HLA class I as a predictor of disease status in chronic human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. A, HLA class I as a predictor of HIV controller status (defined as plasma HIV-1 RNA load ≤2000 copies/mL). B, HLA class I as a predictor of hepatitis B surface antigen (HBsAg) status. C, HLA class I as a predictor of hepatitis B e antigen (HBeAg) status. In A–C, the red line represents analysis with cohort location only as predictor of virologic outcome; the blue line, a prediction incorporating HLA class I genotype plus cohort location. In C, HIV load and CD4 counts were also included in both models. D, HLA class I locus as a predictor of HBeAg status: HLA-A (blue line) versus HLA-B (red line) versus HLA-C (green line). The analysis in D does not correct for CD4⁺ T-cell count or HIV load, so 7 additional patients for whom these data were missing were included. Abbreviation: AUC, area under the curve.